[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4333/KPS.2010.40.S.063

Solid Lipid Nanoparticles as Drug Delivery System for Water-Insoluble Drugs

Li, Rihua (College of Pharmacy, Woosuk University)
Lim, Soo-Jeong (Department of Bioscience and Biotechnology, Sejong University)
Choi, Han-Gon (College of Pharmacy, Hanyang University)
Lee, Mi-Kyung (College of Pharmacy, Woosuk University)

Publication Information

Journal of Pharmaceutical Investigation / v.40, no.spc, 2010 , pp. 63-73 More about this Journal

Abstract

Solid lipid nanoparticles (SLNs) have emerged to combine the advantages of polymeric nanoparticles and lipid emulsions in early 1990s. SLNs can present several desirable properties derived from the solid state core. When formulating SLNs, there should be careful considerations about the physical state of the inner solid lipid core and its polymorphism and supercooling behavior. In this review, SLNs were compared to lipid emulsion and emulsion of supercooled melt to understand the unusual behaviors compared to lipid emulsions and to have insights into stability and release mechanism. SLNs have been regarded as biocompatible system because lipids are usually well-tolerable ingredients than polymers. Several studies showed good tolerability of SLNs in terms of cytotoxicity and hemolysis. Similar to various other nanoparticulate drug delivery systems, SLNs can also change biodistribution of the incorporated drugs in a way to enhance therapeutic effect. Most of all, large scale production of SLNs was extablished wihtout using organic solvents. Although there is no SLN product in the market till date, several advantagious properties of SLNs and the progress we have seen so far would make commercial product of SLNs possible before long and encourage research community to apply SLN-based formulations for water-insoluble drugs.

Keywords

water-insoluble drug; solid lipid nanoparticles; parenteral delivery;

Citations & Related Records

Reference

1	Wong, H.L., Rauth, A.M.,Bendayan, R., Manias, J.L., Ramaswamy, M., Liu, Z., Erhan, S.Z., Wu, X.Y., 2006. A new polymer-lipid hydrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug resistant human breast cancer cells. Pharm. Res. 23, 1574-1585. DOI
2	Xu, Z., Chen, L., Gu, W., Gao, Y., Lin, L., Zhang, Z., Xi, Y., Li, Y., 2009. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials 30, 226-232. DOI
3	Sun, J.Y., Zhou, Z.F., Liu, F., Chen, G.S., 2007. Pharmacokinetics and tissue distribution of oxymatrine-SLN, Chin. Pharm. J. 42, 1091-1095.
4	Tian, J., Pang, X., Yu, K., Liu, L., Zhou, J., 2008. Preparation, characterization and in vivo distribution of solid lipid nanoparticles loaded with cisplatin. Pharmazie 63, 593-597.
5	Trivedi, R., and Kompella, U.B., 2010. Nanomicellar formulations for sustained drug delivery: strategies and underlying principles. Nanomedicine (Lond). 5(3), 485-505. DOI
6	Ugazio, E., Cavali, R., Gasco, M.R., 2002. Incorporation of cyclosporin A in solid lipid nanoparticles (SLN), Int. J. Pharm. 241, 341-344. DOI
7	Van de Manakker, F., Vermonden, T., van Nostrum, C.F., Hennink, W.E., 2009. Cyclodextrin-based polymeric materials: synthesis, properties, and pharmaceutical/biomedical applications. Biomacromolecules. 10(12): 3157-75. DOI
8	Vivek, K., Reddy, H., Murthy, R.S., 2007. Investigations of the effect of the lipid matrix on drug entrapment, in vitro release, and physical stability of olanzapine-loaded solid lipid nanoparticles. AAPS Pharm. Sci. Tech. 8, E83.
9	Wan, F., You, J., Sun, Y., Zhang, X.-G., Cui, F.-D., Du, Y.-Z., Yuan, H., and Hu, F.-Q., 2008. Studies on PEG-modified SLN loading vinorelbine bitartrate (I): preparation and evaluation in vitro, Int. J. Pharm. 359, 104-110. DOI
10	Serpe, L., Guido, M., Canaparo, R., Muntoni, E., Cavalli, R., Panzanelli, P., Della Pepal, C., Bargoni, A., Mauro, A., Gasco, M. R., Eandi, M., and Zara, G. P., 2006. Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines. J. Nanosci. Nanotechnol. 6, 3062-3069. DOI
11	Serpe,L., Catalano, M.G., Cavalli, R., Ugazio, E., Bosco, O., Canaparo, R., Muntoni, E., Frairia, R., Gasco, M.R., Eandi, M. and Zara, G.P., 2004. Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line, Eur. J. Pharm. Biopharm. 58, 673-680. DOI
12	Sharma, P., Ganta, S., Denny, W.A., Garg, S., 2009. Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil. Int. J. Pharm. 367, 187-194. DOI
13	Muller, R.H., Lucks, J.S., 1993. Arzneistofftrager aus festen Lipidteilchen-Feste Lipid Nanospharen (SLN). German Patent Application DE 4131562.
14	Muller, R.H., Runge, S.A., 1998. Solid lipid nanoparticles (SLN $^{\circledR}$ ) for controlled drug delivery. In Submicron emulsions in drug targeting and delivery, Harwood academic publishers, edited by S. Benita., pp. 219-233.
15	Muller, R.H., Ruhl, D., Runge, S. Schulze-Forster, K. and Mehnert, W., 1997. Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant. Pharm. Res. 14, 458-462. DOI
16	Ogawa, Y., 1988. In vivo release profiles of leuprolide acetate from microcapsules with polylactic acids or copoly(lactic/glycolic) acids and in vivo degradation of these polymers. Chem. Pharm. Bull. 36: 2576-2581. DOI ScienceOn
17	Paliwal, R., Rai, S., Vaidya, B., Khatri, K., Goyal, A.K., Mishra, N., Mehta, A., and Vyas, S. P., 2008. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine 5, 184-191.
18	Lim, S.J., Lee, M.K., Kim, C.K., 2004. Altered chemical and biological activities of alltrans retinoic acid incorporated in solid lipid nanoparticle powders, J. Control. Release 100, 53-61. DOI
19	Li, R., Eun, J.S., Lee, M.-K., 2010. Pharmacokinetics and biodistribution of paclitaxel loaded in pegylated solid lipid nanoparticles after intravenous administration. Arch. Pharm. Res. (submitted).
20	Lian, J., Zhang, S., Wang, J., Fang, K., Zhang, Y., Hao, Y., 2008. Novel galactosylated SLN for hepatocyte-selective targeting of floxuridinyl diacetate. J. Drug Target. 16, 250-256. DOI
21	Liu, H., Gong, T., Fu, H.L., Wang, C.G., Wang, X.L., Chen, Q., Zhang, Q., He, Q., Zhang, Z. R., 2008. Solid lipid nanoparticles for pulmonary delivery of insulin. Int. J. Pharm. 356, 333-344. DOI ScienceOn
22	Liu, J., Zhu, J., Du, Z., Qin, B., 2005. Preparation and pharmacokinetic evaluation of Tashinone IIA solid lipid nanoparticles, Drug Dev. Ind. Pharm. 31, 551-556. DOI
23	Liu, K., Sun, J., Wang, Y.J., He, Y., Gao, K., He, Z.G., 2008. Preparation and characterization of 10-hydroxycamptothecin loaded nanostructured lipid carriers. Drug Dev. Ind. Pharm. 34, 465-471. DOI
24	He, C.X., He, Z.G., Gao, J.Q., 2010. Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs. Expert Opin. Drug Deliv. 7(4), 445-60. DOI
25	Hsu, M.H., Su, Y.C., 2008. Iron-oxide embedded solid lipid nanoparticles for magnetically controlled heating and drug delivery. Biomed. Microdevices 10, 785-793. DOI
26	Bi, R., Shao, W., Wang, Q., Zhang, N., 2009. Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery. J. Biomed. Nanotechnol. 5, 84-92. DOI
27	Dianzani, C., Cavalli, R., Zara, G.P., Gallicchio, M., Lombardi, G., Gasco, M.R., Panzanelli, P., Fantozzi, R., 2006. Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells. Br. J. Pharmacol. 148, 648-656. DOI
28	Bhaskar, K., Anbu, J., Ravichandiran, V., Venkateswarlu, V., Rao, Y.M., 2009. Lipid nanoparticles for transdermal delivery of flurbiprofen: Formulation, in vitro, ex vivo and in vivo studies. Lipids Health. Dis. 8, 6. DOI
29	Bhaskar, K., Krishna Mohan, C., Lingam, M., Jagan Mohan, S., Venkateswarlu, V., Madhusudan Rao, Y., Anbu, J., Ravichandran, V., 2009. Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: In vitro and in vivo characteristics. Drug Dev. Ind. Pharm. 35, 98-113. DOI
30	Bondi, M.L., Azzolina, A., Craparo, E.F., Capuano, G., Lampiasi, N., Giammona, G., Cervello, M., 2009. Solid lipid nanoparticles containing nimesulide: Preparation, characterization and cytotoxicity studies. Curr. Nanosci. 5, 39-44. DOI
31	Bondi, M.L., Montana, G., Craparo, E.F., Picone, P., Capuano, G., Carlo, M.D., Giammona, G., 2009. Ferulic acid-loaded lipid nanostructures as drug delivery systems for Alzheimers disease: Preparation, characterization and cytotoxicity studies. Curr. Nanosci. 5, 26-32.
32	Brioschi, A., Zara, G.P., Calderoni, S., Gasco, M.R., Mauro, A., 2008. Cholesteryl butyrate solid lipid nanoparticles as a butyric acid prodrug. Molecules 13, 230-254. DOI
33	Brioschi, A., Zenga, F., Zara, G.P., Gasco, M.R., Ducati, A., Mauro, A., 2007. Solid lipid nanoparticles: Could they help to improve the efficacy of pharmacologic treatments for brain tumors? Neurol. Res. 29, 324-330. DOI
34	Zhang, X., Pan, W., Gan, L., Zhu, C., Gan, Y., Nie, S., 2008. Preparation of a dispersible PEGylate nanostructured lipid carriers (NLC) loaded with 10-hydroxycamptothecin by spray-drying. Chem. Pharm. Bull. (Tokyo) 56, 1645-1650. DOI
35	Battaglia, L., Trotta, M., Gallarate, M., Carlotti, M.E., Zara, G.P., Bargoni, A., 2007. Solid lipid nanoparticles formed by solventin-water emulsion-diffusion technique: Development and influence on insulin stability. J. Microencapsul. 24, 660-672.
36	Zara, G.P., Cavalli, R., Fundarò, A., Bargoni A., Caputo, O., Gasco, M.R., 1999. Pharmacokinetics of doxorubicin incorporated in solid lipid nanosheres (SLN). Pharmacol. Res. 40, 281-286. DOI
37	Zara,G.P., Bargoni, A., Cavalli, R., Fundaro, A., Vighetto, D., Gasco, M.R., 2002. Pharmacokinetics and tissue distribution of idarubicin-loaded solid lipid nanoparticles after duodenal administration to rats. J. Pharm. Sci. 91, 1324-1333. DOI
38	Zhang, D., Ren, T., Lou, H., Xing, J., 2005. The tissue distribution in mice and pharmacokinetics in rabbits of oridonin-solid lipid nanoparticles. Acta Pharm. Sin. 40, 573-576.
39	Zhang, J. Q., Liu, J., Li, Y. L., Jasti, B. R., 2007. Preparation and characterization of solid lipid nanoparticles containing silibinin. Drug Deliv. 14, 381-387. DOI
40	Wang, D., Zhao, P., Cuia, F., Li, X., 2007. Preparation and characterization of solid lipid nanoparticles loaded with total flavones of Hippophae rhamnoides (TFH). PDA J. Pharm. Sci. Technol. 61, 110-120.
41	Wang, J.J., Liu, K.S., Sung, K.C., Tsai, C.Y., Fang, J.Y., 2009. Skin permeation of buprenorphine and its ester prodrugs from lipid nanoparticles: Lipid emulsion, nanostructured lipid carriers and solid lipid nanoparticles. J. Microencapsul. 13, 1-14. DOI
42	Shegokar, R., Singh, K.K., Müller, R.H., 2010. Production & stability of stavudine solid lipid nanoparticles-From lab to industrial scale. Int J Pharm. (in press).
43	Siekmann, B., Westesen, K., 1992. Submicron-sized parenteral carrier systems based on solid lipids. Pharm. Pharmacol. Lett. 1, 123-126.
44	Siekmann, B., Westesen, K., 1994. Thermoanalysis of the recrystallization process of melt-homogenized glyceride nanoparticles., Colloids Surf. B: Biointerfaces 3, 159-175. DOI
45	Siekmann, B., Westesen, K., 1998. Submicron lipid suspensions (solid lipid nanoparticles) versus lipid nanoemulsions: similarities and differences. In Submicron emulsions in drug targeting and delivery, harwood academic publishers, edited by S. Benita., pp. 205-218.
46	Sjostrom, B., Kronberg, B., Carlfors, J., 1993. A method for the preparation of submicron particles of sparingly water-soluble drugs by precipitation in oil-in-water emulsions. I: Influence of emulsification and surfactant concentration. J. Pharm. Sci. 82, 579-583. DOI
47	Smith, A., Hunneyball, M., 1986. Evaluation of poly(lactic acid) as a biodegradable drug delivery system for parenteral administration. Int. J. Pharm. 30, 215-220. DOI ScienceOn
48	Prankerd, R.J. ad Stella, V.J., 1990. The use of oil-in-water emulsions as a vehicle for parenteral drug administration. J. Parent. Sci. Tech. 44, 139-149.
49	Paolicelli, P., Cerreto, F., Cesa, S., Feeney, M., Corrente, F., Marianecci, C., Casadei, M.A., 2008. Influence of the formulation components on the properties of the system SLN-dextran hydrogel for the modified release of drugs. J. Microencapsul. 1-10.
50	Pellizzaro, C., Coradini, D., Morel, S., Ugazio, E., Gasco, M.R., and Daidone, M.G., 1999. Cholesteryl butyrate in solid lipid nanoparticles as an alternative approach for butyric acid delivery, Anticancer Res. 19, 3921-3926.
51	Reddy, L.H., Sharma, R.K., Chuttani,K., Mishra, A.K., Murthy, R.S.R., 2005. Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid nanoparticles in Dalton's lymphoma tumor bearing mice, J. Control. Release 105, 185-198. DOI ScienceOn
52	Liu, W., Hu, M., Xue, C., Xu, H., Yang, X., 2008. Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate. Int. J. Pharm. 364, 135-141. DOI
53	Lu, B., Xiong, S.B., Yang, H., Yin, X.D., Chao, R.B., 2006. Solid lipid nanoparticles of mitoxantrone for local injection against breast cancer and its lymph node metastases. Eur. J. Pharm. Sci. 28, 86-95. DOI
54	Lucks, J.S., Müller, R.H., Konig, B., 1992. Solid lipid nanoaprticles (SLN) – an alternative parenteral drug carrier system. Eur. J. Pharm. Biopharm. 38: 33S.
55	Magenheim, B., Levy, M.Y. and Benita, S., 1993. A new in vitro technique for evaluation of drug release profile from colloidal carriers- ultrafiltration technique at low pressure. Int. J. Pharm. 94, 115-123. DOI
56	Joshi, M., Pathak, S., Sharma, S., Patravale, V., 2008. Design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: Nanoject. Int. J. Pharm. 364, 119-126. DOI
57	Huang, Z.R., Hua, S.C., Yang, Y.L., Fang, J.Y., 2008. Development and evaluation of lipid nanoparticles for camptothecin delivery: a comparison of solid lipid nanoparticles, nanostructured lipid carriers, and lipid emulsion. Acta Pharmacol. Sin. 29(9), 1094-102. DOI
58	Jain, D., Banerjee, R., 2008. Comparison of ciprofloxacin hydrochloride-loaded protein, lipid, and chitosan nanoparticles for drug delivery. J. Biomed. Mater. Res. Part B Appl. Biomater. 86B, 105-112. DOI
59	Janssens, S., Van den Mooter, G., 2009. Review: physical chemistry of solid dispersions. J. Pharm. Pharmacol. 61(12), 1571-86. DOI
60	Kumar, V.V., Chandrasekar, D., Ramakrishna, S., Kishan, V., Rao, Y.M., Diwan, P.V., 2007. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: Influence of wax and glyceride lipids on plasma pharmacokinetics. Int. J. Pharm. 335, 167-175. DOI
61	Kumari, A., Yadav, S.K., Yadav, S.C., 2009. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B. Biointerfaces. 75(1):1-18. DOI
62	Kuo, Y.C., Chen, H.H., 2009. Entrapment and release of saquinavir using novel cationic solid lipid nanoparticles. Int. J. Pharm. 365, 206-213.
63	Dong, X., Mattingly, C.A., Tseng, M., Cho, M., Adams, V.R., Mumper, R. J., 2008. Development of new lipid-based paclitaxel nanoparticles using sequential simplex optimization. Eur. J. Pharm. Biopharm. 72, 9-17. DOI
64	Faisal, S., Baboota, S., Ali, J., Ahuja, A. , 2008. Development and characterization of carvedilol-loaded solid lipid nanoparticles. J. Pharm. Pharmacol. 60, 150.
65	Eldem, T., Speiser, P., and Hincal, A., 1991. Optimization of spraydried and -congealed lipid micropellets and characterization of their surface morphology by scanning electron microscopy. Pharm. Res. 8, 47-54. DOI
66	Elder, D.P., Delaney, E., Teasdale, A., Eyley, S., Reif, V.D., Jacq, K., Facchine, K.L., Oestrich, R.S., Sandra, P., David, F., 2010. The utility of sulfonate salts in drug development. J. Pharm. Sci. 99(7): 2948-61. DOI
67	Esposito, E., Fantin, M., Marti, M., Drechsler, M., Paccamiccio, L., Mariani, P., Sivieri, E., Lain, F., Menegatti, E., Morari, M., Cortesi, R., 2008. Solid lipid nanoparticles as delivery systems for bromocriptine. Pharm. Res. 25, 1521-1530. DOI
68	Fontana, G., Maniscalco, L., Schillaci, D., Cavallaro, G., Giammona, G., 2005. Solid lipid nanoparticles containing tamoxifen characterization and in vitro antitumoral activity, Drug Deliv. 12, 385-392. DOI
69	Fundaro, A., Cavalli, R., Bargoni, A., Vighetto, D., Zara, G.P., Gasco, M.R., 2000. Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after IV administration to rats. Pharm. Res. 42, 337-343. DOI
70	Gallarate, M., Trotta, M., Battaglia, L., Chirio, D., 2008. Preparation of solid lipid nanoparticles from W/O/W emulsions: Preliminary studies on insulin encapsulation. J. Microencapsul. 1-9.
71	Han, F., Li, S.M., Yin, R., Shi, X.L., Jai, Q., 2008. Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen. Drug Dev. Ind. Pharm. 34, 453-458. DOI
72	Yang, S.C., Lu, L.F., Cai, Y., Zhu, Z.B., Liang, B.W., Yang, C.Z., 1999. Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. J. Control. Release 59, 299-307. DOI
73	Yang, L., Geng, Y., Li, H., Zhang, Y., You, J., Chang, Y., 2009. Enhancement the oral bioavailability of praziquantel by incorporation into solid lipid nanoparticles. Pharmazie 64, 86-89.
74	Yang, S., Zhu, J., Lu, Y., Liang, B., Yang, C., 1999. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm. Res. 16, 751-757. DOI
75	Yang, S.C., Zhu, Z.B., 2002. Preparation and characterization of camptothecan solid lipid nanoparticles. Drug Dev. Ind. Pharm. 28, 265-274. DOI
76	Ye, J., Wang, Q., Zhou, X., Zhang, N., 2008. Injectable actaritloaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis. Int. J. Pharm. 352, 273-279. DOI
77	Ying, X.Y., Du, Y.Z., Chen, W.W., Yuan, H., Hu, F.Q., 2008. Preparation and characterization of modified lipid nanoparticles for doxorubicin controlled release. Pharmazie 63, 878-882.
78	Yu, B.T., Zhang, Z.R., Zeng, R.J., 2000. Study on the liver targeted 5-fluorouracil solid lipid nanoparticles. Yaoxue Xuebao 35, 704-705.
79	Yuan, H., Miao, J., Du, Y.Z., You, J., Hu, F.Q., Zeng, S., 2008. Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. Int. J. Pharm. 348, 137-145. DOI
80	Zara, G.P., Cavalli, R., Bargoni, A., Fundarò, A., Vighetto, D., Gasco, M.R., 2002. Intravenous administration to rabbits of non-stealth and stealth doxorubicin-loaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other tissues. J. Drug Target. 10(4), 327-35. DOI
81	Wang, J.X., Sun, X., Zhang, Z.R., 2002. Enhanced brain targeting by synthesis of 3-,5-dioctanoyl-5-fluoro-2-deoxyuridine and incorporation into solid lipid nanoparticles. Eur. J. Pharm. Biopharm. 54, 285-290. DOI
82	Westesen, K., Bunjes, H., 1995. Do nanoparticles prepared from lipids solid at room temperature always possess a solid lipid matrix ? Int. J. Pharm. 115, 129-131. DOI
83	Westesen, K., Siekmann, B., 1997. Investigation of the gel formation of phospholipid-stabilized solid nanoparticles. Int. J. Pharm. 151, 35-45. DOI
84	Williams, J., Lansdown, R., Sweitzer, R., Romanoswki, M., Labell, R., Ramaswami, R., Unger, E., 2003. Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors. J. Control. Release 91, 167-172. DOI
85	Wong, H.L., Bendayan, R., Rauth, A.M., Xue, H.Y., Babakhanian, K., Wu, X.Y., 2006. A mechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle (PLN) system. J. Pharmacol. Exp. Ther. 317, 1372-1381. DOI
86	Wong, H.L., Bendayan, R., Rauth, A.M., Wu, X.Y., 2004. Development of solid lipid nanoparticles containing ionically-complexed chemotherapeutic drugs and chemosensitizers. J. Pharm. Sci. 93, 1993-2004. DOI
87	Strickley, R.G., 2004. Solubilizing excipients in oral and injectable formulations. Pharm. Res. 21(2), 201-30. DOI
88	Souto E.B., Müller RH., 2010. Lipid nanoparticles: effect on bioavailability and pharmacokinetic changes. Handb. Exp. Pharmacol. 197, 115-41. DOI
89	Speiser, P., 1990. Lipidnanopellets als Tragersystem fur Arzneimettel zur peroralen Anwendung., European Patent, EP 0167825.
90	Stevens, P.J., Sekido, M., Lee, R.J., 2004. A folate-receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug, Pharm. Res. 21, 2153-2157. DOI
91	Reddy, L.H., Vivek, K., Bakshi, N., Murthy, R.S., 2006. Tamoxifen citrate loaded solid lipid nanoparticles (SLN): preparation, characterization, in vitro drug release, and pharmacokinetic evaluation, Pharm. Dev. Technol. 11, 167-177. DOI
92	Ruckmani, K., Sivakumar, M., Ganeshkumar, P.A., 2006. Methotrexate loaded solid lipid nanoparticles (SLN) for effective treatment of carcinoma. J. Nanosci. Nanotechnol. 6, 2991–2995.
93	Sanjula, B., Shah, F.M., Javed, A., and Alka, A., 2009. Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement. J. Drug Target. 17, 249-256. DOI
94	Sarmento, B., Martins, S., Ferreira, D., and Souto, E.B., 2007. Oral insulin delivery by means of solid lipid nanoparticles. Int. J. Nanomedicine 2, 743-749.
95	Schwartz, C., Mehnert, J.S. Lucks, J.S., Muller, R.H., 1994. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J. Control. Rel. 30, 83-96. DOI
96	Mirtallo, J.M., Dasta, J.F., Kleinschmidt, K.C., Varon, J., 2010. State of the art review: Intravenous fat emulsions: Current applications, safety profile, and clinical implications. Ann. Pharmacother. 44(4):688-700. DOI
97	Mallick, S., Pattnaik, S., Swain, K., De, P.K., 2007. Current perspectives of solubilization: potential for improved bioavailability. Drug Dev. Ind. Pharm. 33(8):865-73. DOI
98	Manjunath, K., Venkateswarlu, V., 2006. Pharmacokinetics, tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration. J. Drug Target. 14, 632-645. DOI
99	Martins, S., Silva, A.C., Ferreira, D.C., Souto, E.B., 2009. Improving oral absorption of samon calcitonin by trimyristin lipid nanoparticles. J. Biomed. Nanotechnol. 5, 76-83. DOI
100	Mller, R.H., Runge, S.A., Ravelli, V., Thunemann, A.F., Mehnert, W., Souto, E.B., 2008. Cyclosporine-loaded solid lipid nanoparticles (SLN): Drug-lipid physicochemical interactions and characterization of drug incorporation. Eur. J. Pharm. Biopharm. 68, 535-544. DOI ScienceOn
101	Kuo, Y.C., Su, F.L., 2007. Transport of stavudine, delavirdine, and saquinavir across the blood-brain barrier by polybutylcyanoacrylate, methylmethacrylate-sulfopropylmethacrylate, and solid lipid nanoparticles. Int. J. Pharm. 340, 143-152. DOI
102	Lee, M.K., Lim, S.J., Kim, C.K., 2007. Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials. 28(12), 2137-46. DOI
103	Li, H.L., Zhao, X.B., Ma, Y.K., Zhai, G.X., Li, L.B., Lou, H.X., 2009. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J. Control. Release 133, 238-244. DOI ScienceOn
104	Cavalli, R., Marengo, E., Rodriguez, L., Gasco, M.R., 1996. Effects of some experimental factors on the production process of solid lipid nanoparticles. Eur. J. Pharm. Biopharm. 42, 110-115.
105	Casadei, M.A., Cerreto, F., Cesa, S., Giannuzzo, M., Feeney, M., Marianecci, C., Paolicelli, P., 2006. Solid lipid nanoparticles incorporated in dextran hydrogels: A new drug delivery system for oral formulations. Int. J. Pharm. 325, 140-146. DOI
106	Cavalli, R., Caputo, O., Gasco, M.R., 1993. Solid lipospheres of doxorubicin and idarubicin, Int. J. Pharm. 89, R9-R12. DOI
107	Cavalli, R., Caputo, O., Gasco, M.R., 2000. Preparation and characterization of solid lipid nanospheres containing paclitaxel, Eur. J. Pharm. Sci. 10, 305-309. DOI
108	Chen, H., Khemtong, C., Yang, X., Chang, X., Gao, J., 2010. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today. (in press).
109	Chen, D.B., Yang, T.Z., Lu, W.L., Zhang, Q., 2001. In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel, Chem. Pharm. Bull. 49, 1444-1447. DOI
110	Collins-Gold, L.C., Lyons, R.T., Bartholow, L.C., 1990. Parenteral emulsions for drug delivery. Adv. Drug. Deliv. Rev. 5, 189-208. DOI
111	Cukierman, E., Khan, D.R., 2010. The benefits and challenges associated with the use of drug delivery systems in cancer therapy. Biochem. Pharmacol. 80(5), 762-70. DOI
112	de Ven, H. V., Vermeersch, M., Shunmugaperumal, T., Vandervoort, J., Maes, L., Ludwig, A., 2009. Solid lipid nanoparticle (SLN) formulations as a potential tool for the reduction of cytotoxicity of saponins. Pharmazie 64, 172-176.
113	Bargoni, A., Cavalli, R., Zara, G.P., Fundaro, A., Caputo, O., Gasco, M.R., 2001. Transmucosal transport of tobramycin incorporated in solid lipid nanoparticles (SLN) after duodenal administration to rats. Part II-tissue distribution, Pharmacol. Res. 43, 497-502. DOI ScienceOn
114	Bunjes, H., Westesen, K. and Koch, M.H.J., 1996. Crystallization tendency and polymorphic transitions in triglyceride nanoparticles. Int. J. Pharm. 129, 159-173. DOI
115	Abdelbary, G., Fahmy, R.H., 2009. Diazepam-loaded solid lipid nanoparticles: Design and characterization. AAPS Pharm-SciTech 10, 211–219.